Morpholine → 3(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid

HRID 613863Notes

Reaction equation

HRID 613863 reaction equation
C([O:4][C:5](=[O:36])[CH2:6][C@@H:7]([N:20]1[CH:24]=[CH:23][C:22]([C:25](=[O:35])[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][CH:28]=2)=[CH:21]1)[C:8]([NH:10][C@H:11]([C:16](=[O:19])[NH:17][CH3:18])[C:12]([CH3:15])([CH3:14])[CH3:13])=[O:9])C=C.N1CCOCC1>C(#N)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:33]([C:30]1[CH:31]=[CH:32][C:27]([CH2:26][C:25]([C:22]2[CH:23]=[CH:24][N:20]([C@@H:7]([C:8]([NH:10][C@H:11]([C:16](=[O:19])[NH:17][CH3:18])[C:12]([CH3:15])([CH3:13])[CH3:14])=[O:9])[CH2:6][C:5]([OH:36])=[O:4])[CH:21]=2)=[O:35])=[CH:28][CH:29]=1)#[N:34]

Participants

5

Reactant 2

HCID 8083MorpholineHCID 700987653(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid allyl ester

Product 1

HCID 539761643(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acidYield 107.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

Routine allyl ester cleavage conditions were previously described by Friedrich-Bochnitschek, S.; Waldmann, H.; Kunz, H. J. Org. Chem. 1989, 54, 751-756. To a solution of 3(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid allyl ester (247 mg, 0.501 mmol) in acetonitrile (2 mL) was added in succession Pd(PPh3)4 (29 mg, 0.026 mmol) and morpholine (226 μL, 2.60 mmol). The resultant mixture was carefully purged with argon. After 30 min, the resultant green mixture was stirred with 10% aqueous KHSO4 (20 mL) and extracted with CHCl3 (35 mL). The organic layer was washed with 10% aqueous KHSO4 (20 mL), dried over Na2SO4, and concentrated. Flash column chromatography with 1% HOAc/3% MeOH/CHCl3 and drying via azeotrope with n-heptane gave 243 mg (94%) of 3(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid as a yellow solid. 1H NMR (CD3OD): δ 8.09 (d, 1H, J=8.7 Hz), 8.05 (dd, 1H, J=2.8, 6.9 Hz), 7.78 (dd, 1H, J=1.9, 1.9 Hz), 7.66 (d, 2H, J=8.4 Hz), 7.46 (d, 2H, J=8.4 Hz), 6.90 (dd, 1H, J=2.2, 2.2 Hz), 6.59 (dd, J=1.9, 3.1 Hz), 5.33 (t, 1H, J=7.5 Hz), 4.22-4.15 (m, 3H), 3.24 (t, 1H, J=8.7 Hz), 2.98 (dd, 1H, J=5.3, 17.4 Hz), 2.66 (d, 3H, J=4.7 Hz), 0.99 (s, 9H). IR (KBr): 3332, 2696, 2230, 1719, 1654, 1532, 1412, 1177 cm-1. HRFABMS: Calculated for C24H29N4O5 (M+H+): 453.2125. Found: 453.2125. Anal. Calculated for C24H28N4O5.0.5 HOAc.0.3 CHCl3 : C, 58.62; H, 5.89; N, 10.81. Found: C, 58.41; H, 5.72; N, 10.50.

Workup

  1. customThe resultant mixture was carefully purged with argon
  2. extractionextracted with CHCl3 (35 mL)
  3. washThe organic layer was washed with 10% aqueous KHSO4 (20 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. dry with materialFlash column chromatography with 1% HOAc/3% MeOH/CHCl3 and drying via azeotrope with n-heptane

Sources & evidence

ORD record
ord-41271cd679e242aea6c7d6de1cdbffff
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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